7th Annual Symposium
Physics of Cancer
Leipzig, Germany
October 4-6, 2016
Invited Talk
Cancer Metastasis in Bone: Investigating the Role of Cancer Cell Interaction with Bone Matrix Proteins and Mesenchymal Stem Cells on the Single Cell Level
Ediz Sariisik1,2,3,4, Stefanie Sudhop1,2,3, Domenik Zistl2,3, Daniela Padula2,3, Cvetan Popov3,4, Jan Oper3,4, Cem Saracel1,6, Matthias Schieker1,5, Denitsa Docheva1,5, Arndt Schilling1,6, Martin Benoit3,4, Hauke Clausen-Schaumann1,2,3
1Center for Applied Tissue Engineering and Regenerative Medicine – CANTER, Munich University of Applied Sciences, Munich, Germany
2Department of Applied Sciences and Mechatronics, Munich University of Applied Sciences, Munich, Germany
3Center for NanoScience, Ludwig-Maximilians-University, Munich, Germany
4Chair of Biophysics and New Materials, Ludwig-Maximilians-University, Munich, Germany
5Experimental Surgery and Regenerative Medicine, Department of Sugery, Ludwig-Maximilians-University, Munich, Germany
6Experimental Plastic Surgery, Clinic for Plasic and Hand Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich Germany
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For some of the most common cancer types, including prostate cancer and breast cancer, the formation of bone metastases is a frequent complication. The spread of the cancer cells into the skeleton is associated with a poor prognosis for the patient. Although the molecular mechanisms of cancer cell growth in the bone microenvironment have been an area of active investigation, the initial steps of tumor cell-to-bone interaction, that lead to cancer cell colonization, remain to be elucidated. In any case, a complex, bidirectional interplay between cancer cells with bone matrix proteins and with cell types residing in the bone tissue is supposed to be involved: Cancer cells express adhesion molecules (e. g. Integrins) that may facilitate their interaction with bone matrix proteins and therefore contribute to their invasive capability and progression into the bone. These adhesion molecules may also play a role in cross-talk between tumor cells with mesenchymal stem cells (MSC) residing in the bone marrow. It is assumed, that MSCs stimulate the invasion of tumor cells into the bone by remodeling the bone microenvironment and thus creating a physical space where the cancer cells can enter. In this study we investigated the adhesive capacity of the two prostate carcinoma cell lines PC3 (bone marrow specific) and LnCAP (lymph node specific). Using atomic force microscopy (AFM) based force spectroscopy, the adhesion patterns on bone-marrow derived stem cells (SCP1) and collagen type I, the major bone matrix protein, for both cell line have been analyzed. PC3 cells have a higher affinity to SCP1 cells as well as to collagen type I compared to LnCAP cells. By β1-Integrin-antibody-blocking the adhesion events were reduced, indication a role of these adhesion molecules in cancer cell-to-bone interaction.

An additional factor that may have influence metastasis development might be the mineralization state of the bone tissue. In case of breast cancer, epidemiological studies have correlated calcium and/or vitamin deficiencies in patients with increased tumor metastatic growth. On the other hand, Vitamin D treatment increases survival rates and prolongs disease-free intervals of the patients. The biological mechanisms underlying the effect of Vitamin D in cancer therapy is not well understood. Recent studies mainly focused on the response of cancer cells on Vitamin D treatment. In contrast, we put the effect of Vitamin D on bone mineralization to the fore and investigated the adhesion of the invasive and non-invasive breast cancer cell lines MDA-MB-231 and MCF-7 on poorly mineralized matrix compared to mineralized matrix.
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